Correlation between gene mutation status and selected clinical features
Overview
Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 7 genes and 3 clinical features across 196 patients, 3 significant findings detected with Q value < 0.25.

  • DNMT3A mutation correlated to 'Time to Death'.

  • U2AF1 mutation correlated to 'AGE'.

  • IDH2 mutation correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 7 genes and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Clinical
Features
Time
to
Death
AGE GENDER
nMutated (%) nWild-Type logrank test t-test Fisher's exact test
DNMT3A 51 (26%) 145 0.000647
(0.0129)
0.0653
(1.00)
0.328
(1.00)
U2AF1 8 (4%) 188 0.591
(1.00)
0.00137
(0.026)
0.0703
(1.00)
IDH2 20 (10%) 176 0.414
(1.00)
1.11e-05
(0.000233)
0.815
(1.00)
FLT3 56 (29%) 140 0.132
(1.00)
0.563
(1.00)
0.754
(1.00)
IDH1 19 (10%) 177 0.627
(1.00)
0.304
(1.00)
0.633
(1.00)
NPM1 54 (28%) 142 0.0927
(1.00)
0.968
(1.00)
0.262
(1.00)
NRAS 15 (8%) 181 0.88
(1.00)
0.287
(1.00)
1
(1.00)
'DNMT3A MUTATION STATUS' versus 'Time to Death'

P value = 0.000647 (logrank test), Q value = 0.013

Table S1.  Gene #1: 'DNMT3A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 170 105 0.9 - 94.1 (12.0)
DNMT3A MUTATED 45 34 0.9 - 37.0 (9.0)
DNMT3A WILD-TYPE 125 71 0.9 - 94.1 (15.0)

Figure S1.  Get High-res Image Gene #1: 'DNMT3A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'U2AF1 MUTATION STATUS' versus 'AGE'

P value = 0.00137 (t-test), Q value = 0.026

Table S2.  Gene #2: 'U2AF1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 196 55.1 (16.2)
U2AF1 MUTATED 8 69.9 (9.0)
U2AF1 WILD-TYPE 188 54.5 (16.1)

Figure S2.  Get High-res Image Gene #2: 'U2AF1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'IDH2 MUTATION STATUS' versus 'AGE'

P value = 1.11e-05 (t-test), Q value = 0.00023

Table S3.  Gene #4: 'IDH2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 196 55.1 (16.2)
IDH2 MUTATED 20 64.8 (8.0)
IDH2 WILD-TYPE 176 54.0 (16.5)

Figure S3.  Get High-res Image Gene #4: 'IDH2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input
  • Mutation data file = LAML-TB.mutsig.cluster.txt

  • Clinical data file = LAML-TB.clin.merged.picked.txt

  • Number of patients = 196

  • Number of significantly mutated genes = 7

  • Number of selected clinical features = 3

  • Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[4] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)